Chlamydia trachomatis is one of the most common pathogens involved in sexually transmitted diseases. In most instances, particularly in women, the infection is asymptomatic and thus, therapeutic measures cannot be initiated. Even in symptomatic cases, unless adequate therapy is implemented in a timely fashion, the patient may end up suffering from long term sequelae including chronic abdominal pain, ectopic pregnancy and infertility. In this proposal we want to test the hypothesis that a vaccine consisting of the C. trachomatis major outer membrane protein (MOMP) will be able to induce protection in mice against a genital challenge with the C. trachomatis mouse pneumonitis (MoPn) biovar. To achieve this goal we want to utilize a MOMP preparation extracted from native organisms that following purification, has been refolded. Adjuvants, that can be utilized in humans, including CpG, ISCOM, Montanide and DNA plasmids will be tested in mice for their ability to enhance the immunogenicity of the MOMP. In addition, in an effort to optimize a protective immune response, we will test different routes of vaccination. In the immunized animals we will be assessing the parameters that are critical for protection using different approaches. We will first compare the immune response in protected and control groups of three different strains of mice, and will attempt to identify epitopes of the MOMP recognized by B and T cells. Another group of immunocompetent animals will be first immunized with MOMP and subsequently, will be treated with antibodies to block CD4+ and CD8+ T cells and B cells before they are challenged. In addition, we will transfer CD4+ and CD8+ T cells and B cells and antibodies from immunized mice to naive animals before they are challenged. Also, we will use anti-ML-12 and anti-IL-4 antibodies to characterize the role that Th1 and Th2 cells have in protection. Furthermore, to identify the cytokines involved in the eradication of Chlamydia, MOMP-immunized mice will be treated with anti-IFN-g and anti-TNF-a antibodies before they are challenged. In conclusion, our goals are to establish an immunization protocol, utilizing a purified and folded MOMP preparation, that can protect mice against a genital challenge, and to characterize the immune components induced by the folded MOMP that are critical for protection.